Article
Engineering, Biomedical
Kevin M. Beussman, Molly Y. Mollica, Andrea Leonarda, Jeffrey Milesc, John Hocterd, Zizhen Songe, Moritz Stollac, Sangyoon J. Hang, Ashley Emerya, Wendy E. Thomasb, Nathan J. Sniadecki
Summary: Measuring cellular traction forces is important for understanding cell behavior and function. A technique called 'black dots' was developed to measure cellular traction forces without altering cell shape or detaching the cells. By evaluating human platelets, the study found that platelets exerting more force have larger spread area, more circular shape, and more uniformly distributed F-actin filaments.
ACTA BIOMATERIALIA
(2023)
Article
Nanoscience & Nanotechnology
Dimitris Missirlis, Miguel Banos, Felix Lussier, Joachim P. Spatz
Summary: In this study, a micropatterning strategy was proposed to introduce small molecules and ligands on patterns of arbitrary shapes on the surface of poly(acrylamide)-based hydrogels. The advantages of this approach include easy use, no need for prefabricated photomasks, the use of mild UV light and biocompatible bioconjugation chemistries, and the ability to pattern low-molecular-weight ligands. Cell patterning experiments demonstrated the response of cells to the combination of pattern shape and substrate elasticity.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Abbas Mgharbel, Camille Migdal, Nicolas Bouchonville, Paul Dupenloup, David Fuard, Eline Lopez-Soler, Caterina Tomba, Marie Courcon, Danielle Gulino-Debrac, Helene Delanoe-Ayari, Alice Nicolas
Summary: Cell rigidity sensing is a basic cellular process that allows cells to adapt to mechanical cues by adjusting the level of stress. Researchers have developed an efficient method to design micron-scale stiffness patterns and a surface coating protocol to tune the density of adhesion proteins, providing tools for cells to exert force on their surroundings. These findings enhance our understanding of the contribution of stiffness alterations in diseases.
Article
Pharmacology & Pharmacy
Sultan Ahmed, Robert. T. Johnson, Reesha Solanki, Teclino Afewerki, Finn Wostear, Derek. T. Warren
Summary: In this study, we developed a VSMC contractility assay using polyacrylamide hydrogels that mimic the physiological stiffness of the aortic wall. We found that changes in VSMC morphology and actomyosin activity are core components of the contractile response. Additionally, we demonstrated that microtubule stability is essential for VSMC contractility.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Thomas Schlichthaerle, Caroline Lindner, Ralf Jungmann
Summary: Cell-extracellular matrix sensing plays a crucial role in cellular behavior and leads to the formation of a macromolecular protein complex called the focal adhesion. Despite their importance in cellular decision making, relatively little is known about cell-matrix interactions and the intracellular transduction of an initial ligand-receptor binding event on the single-molecule level. Here, authors combine ligand-decorated DNA tension sensors with DNA-PAINT super-resolution microscopy to study the mechanical engagement of single integrin receptors and the downstream influence on actin bundling.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Farah Mustapha, Kheya Sengupta, Pierre-Henri Puech
Summary: Force is an important parameter for cells to adapt to their microenvironment. T lymphocytes use mechano-sensitivity to recognize antigens and carry out immune functions. Traction force microscopy is a technique that has gained interest in the ImmunoBiophysics community for measuring forces exerted by immune cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Zachary W. Lipsky, Guy K. German
Summary: Biological tissues are structurally heterogeneous at the microscale, and macroscopic testing techniques cannot accurately measure the impact of this heterogeneity on the mechanical properties of the tissue. The study results demonstrate that differences in crack propagation pathways are the cause of large variability in mechanical work of fracture between macroscopic samples.
ACTA BIOMATERIALIA
(2021)
Review
Microscopy
Malgorzata Lekka, Kajangi Gnanachandran, Andrzej Kubiak, Tomasz Zielinski, Joanna Zemla
Summary: Cells generate mechanical forces when interacting with the extracellular matrix or neighbouring cells. Techniques like traction force microscopy have been developed to measure these forces and understand how cells sense, adapt, and respond to mechanical forces, revealing their role in controlling and regulating cell behavior in normal and pathological conditions.
Article
Multidisciplinary Sciences
Soliman Alhudaithy, Kazunori Hoshino
Summary: This study introduces a novel biocompatible PDMS-based micromechanical tweezers (mu Tweezers) that can characterize and manipulate hydrogel-based organoids. The mu Tweezers significantly reduce the volume of valuable hydrogels used for testing, making it ideal for high-throughput measurement of micro-mesoscale 3D cell cultures. The proposed method shows great potential in the biomedical, biochemical, and regenerative engineering fields. The stiffness changes of collagen I hydrogel organoids were measured, and it was found that the SKOV3-embedded organoids had more shrinkage and lowered moduli compared to the control group.
Editorial Material
Multidisciplinary Sciences
Kseniya Korobchevskaya, Huw Colin-York, Liliana Barbieri, Marco Fritzsche
Summary: Three novel TFM approaches are proposed in combination with total internal reflection, structured illumination microscopy, and astigmatism, improving spatial and temporal performance in mechanical force quantification in either two-dimensional or three-dimensional settings, while maintaining low illumination powers.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Alexandros Afthinos, Kaustav Bera, Junjie Chen, Altug Ozcelikkale, Alice Amitrano, Mohammad Ikbal Choudhury, Randy Huang, Pavlos Pachidis, Panagiotis Mistriotis, Yun Chen, Konstantinos Konstantopoulos
Summary: In this study, we developed polyacrylamide-based microchannels with physiological stiffness and prescribed dimensions for high-throughput analysis of cell migration. We found a biphasic dependence of cell speed on confinement and stiffness. By utilizing novel four-walled microchannels, we revealed the distinct contributions of apicolateral and basal microchannel wall stiffness to confined and unconfined migration. We also innovated three-dimensional traction force measurements around spatially confining cells at subcellular resolution by tracking nanobeads embedded within the channel walls.
Article
Chemistry, Multidisciplinary
Morteza Aramesh, Simon Mergenthal, Marcel Issler, Birgit Plochberger, Florian Weber, Xiao-Hua Qin, Robert Liska, Georg N. Duda, Johannes B. Huppa, Jonas Ries, Gerhard J. Schuetz, Enrico Klotzsch
Summary: The study developed a traction force microscopy platform to quantify the forces exerted by T-cell microvilli during activation, and confirmed the interaction with specific T-cell activating antibodies fixed on marker beads. Cellular components like actin, TCR, and CD45 were found to rearrange upon interaction, with actin forming a vortex-like structure around beads, TCR enrichment at bead surface, and CD45 exclusion from bead-microvilli contacts.
Article
Multidisciplinary Sciences
Andrew T. Meek, Nils M. Kronenberg, Andrew Morton, Philipp Liehm, Jan Murawski, Eleni Dalaka, Jonathan H. Booth, Simon J. Powis, Malte C. Gather
Summary: The authors introduce an interference-based method illuminated by two rapidly alternating wavelengths for real-time mapping of nanoscale forces with sub-second mechanical fluctuations. This technique allows monitoring of cellular forces with high throughput and excellent temporal resolution, providing a new approach for studying dynamic processes in mechanobiology.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Nafsika Chala, Xinyu Zhang, Tomaso Zambelli, Ziyi Zhang, Teseo Schneider, Daniele Panozzo, Dimos Poulikakos, Aldo Ferrari
Summary: Mechanical signals establish communication between mammalian cells and their environment. Cells exert forces and transmit them at focal adhesion points. External stimuli affect the adhesion-free cell surface. The integration of Fluidic Force Microscopy and confocal Traction Force Microscopy enables precise force probing of individual cells, allowing the investigation of cellular mechanisms in response to mechanical stimuli.
Article
Engineering, Biomedical
Michal Levin, Megan T. Valentine, Noy Cohen
Summary: Hydrogels are hydrophilic polymer networks that swell in water and have a wide range of applications. This study investigates the equilibrium mechanical responses of hydrogel-based shells filled with a liquid core, showing that the shell geometry and core composition can influence the mechanical response of the structure. The results provide guidance for designing novel core-shell structures with tunable properties and mechanical responses.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2021)
Article
Cell & Tissue Engineering
Robin E. Wilson, Aleksandra K. Denisin, Alexander R. Dunn, Beth L. Pruitt
Summary: Cell structure and migration are influenced by the mechanical properties and geometry of the cell adhesive environment. This study developed microwell platforms to investigate the effects of 2D vs. 3D geometries on single-cell F-actin and nuclear organization. The results showed that both 3D confinement and adhesive environment influenced actin and nuclear structure in single cells.
CELLULAR AND MOLECULAR BIOENGINEERING
(2021)
Review
Medicine, Research & Experimental
Keri Dame, Alexandre J. S. Ribeiro
Summary: Current models predicting drug adverse effects often fail due to the variability of iPSC-derived hepatic and cardiac cells, which do not fully mimic adult primary tissues. Microfluidic systems have potential to improve differentiation protocols and enhance the physiological relevance of iPSC-derived cells, aiding in drug development programs. Further development and standardization of technologies can lead to more accurate in vitro models for evaluating drug effects.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Medicine, Research & Experimental
Andres Rubiano, Amruta Indapurkar, Ryosuke Yokosawa, Alina Miedzik, Barry Rosenzweig, Ayesha Arefin, Chloe M. Moulin, Keri Dame, Neil Hartman, Donna A. Volpe, Murali K. Matta, David J. Hughes, David G. Strauss, Tomasz Kostrzewski, Alexandre J. S. Ribeiro
Summary: The study characterized the reproducibility of liver microphysiological systems (MPSs) in predicting hepatic drug effects through experiments on drug toxicity, metabolism, and intracellular accumulation. The results demonstrated that the liver MPS can reliably produce consistent experimental outcomes for drug evaluation applications, showing better stability and functionality compared to other culture platforms. The study also provided general considerations and recommendations for using liver MPSs in drug development.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Orlando Chirikian, William R. Goodyer, Elda Dzilic, Vahid Serpooshan, Jan W. Buikema, Wesley McKeithan, HaoDi Wu, Guang Li, Soah Lee, Markus Merk, Francisco Galdos, Aimee Beck, Alexandre J. S. Ribeiro, Sharon Paige, Mark Mercola, Joseph C. Wu, Beth L. Pruitt, Sean M. Wu
Summary: The study introduced a method for creating chamber-specific reporter hiPSC lines using CRISPR-Cas9 technology, successfully isolating ventricular and atrial-like CMs. These genetic tools provide a new platform for research and treatment specific to cardiac diseases.
SCIENTIFIC REPORTS
(2021)
Review
Medicine, Research & Experimental
Hongbing Wang, Paul C. Brown, Edwin C. Y. Chow, Lorna Ewart, Stephen S. Ferguson, Suzanne Fitzpatrick, Benjamin S. Freedman, Grace L. Guo, William Hedrich, Scott Heyward, James Hickman, Nina Isoherranen, Albert P. Li, Qi Liu, Shannon M. Mumenthaler, James Polli, William R. Proctor, Alexandre Ribeiro, Jian-Ying Wang, Ronald L. Wange, Shiew-Mei Huang
Summary: Nonclinical testing is crucial for evaluating potential risks and effectiveness of new drugs. Current 2D in vitro systems lack accuracy in simulating in vivo processes, while animal studies have limitations. Researchers are developing novel 3D models to improve drug safety and efficacy predictions.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Cell & Tissue Engineering
Kevin C. Hart, Joo Yong Sim, Matthew A. Hopcroft, Daniel J. Cohen, Jiongyi Tan, W. James Nelson, Beth L. Pruitt
Summary: This paper introduces a simple and low-cost uniaxial stretching device, as well as a pressure controller, which can be used to study cell movement under external mechanical forces. The device demonstrates the mechanical regulation of collective cell movements in epithelia.
CELLULAR AND MOLECULAR BIOENGINEERING
(2021)
Article
Pharmacology & Pharmacy
Hisham Qosa, J. S. Alexandre Ribeiro, R. Neil Hartman, A. Donna Volpe
Summary: The study assessed the similarities and differences between iPSC-heps and Prim-heps in drug metabolism, hepatotoxicity, and drug transport. While all culture models showed similar basal CYP activity, Prim-heps were generally more sensitive to CYP inducing agents. iPSC-heps appear useful for toxicity and transport studies, but may not be optimal for metabolism studies.
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2021)
Article
Cell & Tissue Engineering
Alex C. Y. Chang, Gaspard Pardon, Andrew C. H. Chang, Haodi Wu, Sang-Ging Ong, Asuka Eguchi, Sara Ancel, Colin Holbrook, John Ramunas, Alexandre J. S. Ribeiro, Edward L. LaGory, Honghui Wang, Kassie Koleckar, Amato Giaccia, David L. Mack, Martin K. Childers, Chris Denning, John W. Day, Joseph C. Wu, Beth L. Pruitt, Helen M. Blau
Summary: This study used human induced pluripotent stem cell-derived cardiomyocytes to reveal deficits in force generation, aberrant calcium handling, and increased reactive oxygen species levels in Duchenne muscular dystrophy (DMD) cardiomyocytes. The research found that progressive post-mitotic telomere shortening in DMD cardiomyocytes is associated with downregulation of shelterin complex and activation of the p53 DNA damage response.
Review
Medicine, Research & Experimental
Elke Anklam, Martin Iain Bahl, Robert Ball, Richard D. Beger, Jonathan Cohen, Suzanne Fitzpatrick, Philippe Girard, Blanka Halamoda-Kenzaoui, Denise Hinton, Akihiko Hirose, Arnd Hoeveler, Masamitsu Honma, Marta Hugas, Seichi Ishida, George En Kass, Hajime Kojima, Ira Krefting, Serguei Liachenko, Yan Liu, Shane Masters, Uwe Marx, Timothy McCarthy, Tim Mercer, Anil Patri, Carmen Pelaez, Munir Pirmohamed, Stefan Platz, Alexandre J. S. Ribeiro, Joseph Rodricks, Ivan Rusyn, Reza M. Salek, Reinhilde Schoonjans, Primal Silva, Clive N. Svendsen, Susan Sumner, Kyung Sung, Danilo Tagle, Li Tong, Weida Tong, Janny Van den Eijnden-van-Raaij, Neil Vary, Tao Wang, John Waterton, May Wang, Hairuo Wen, David Wishart, Yinyin Yuan, William Jr Jr Slikker
Summary: There is a growing need for safety assessment of food, drugs, and personal care products, driven by the utilization of emerging cellular, molecular, and in silico technologies. The rapid advancement and convergence of these technologies may impact regulatory decisions and approvals, but the lack of thorough evaluation raises concerns about their readiness for regulatory application. Developing strategies to evaluate these new technologies and ensuring their appropriate and rapid incorporation into regulatory use is crucial for the regulatory science field to keep pace with advancements and prepare for emerging global challenges. Collaboration between the regulatory community and technology developers is essential to harness collective capabilities for evaluating new assessment tools effectively.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Medicine, Research & Experimental
Szczepan W. Baran, Paul C. Brown, Andreas R. Baudy, Suzanne C. Fitzpatrick, Christopher Frantz, Aaron Fullerton, Jinping Gan, Rhiannon N. Hardwick, Kathleen M. Hillgren, Anna K. Kopec, Jennifer L. Liras, Donna L. Mendrick, Ryan Nagao, William R. Proctor, Diane Ramsden, Alexandre J. S. Ribeiro, David Stresser, Kyung E. Sung, Radhakrishna Sura, Kazuhiro Tetsuka, Lindsay Tomlinson, Terry Van Vleet, Matthew P. Wagoner, Qin Wang, Sevim Yildiz Arslan, Gorm Yoder, Jason E. Ekert
Summary: This article discusses the output from a workshop between FDA and IQ MPS Affiliate on the application of complex in vitro models in pharmaceutical drug development. The workshop aimed to identify barriers to the adoption of microphysiological systems (MPS) technologies and to address evaluation/qualification pathways. The output includes a working definition of MPS, detailed description of case studies, and analysis of breakout sessions.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Article
Chemistry, Analytical
Anna A. Kim, Erica A. Castillo, Kerry Lane, Gabriela Torres, Orlando Chirikian, Robin E. Wilson, Sydney A. Lance, Gaspard Pardon, Beth L. Pruitt
Summary: This study presents a method to fabricate large-batch generation of microenvironment protein templates on glass chips, which increases efficiency and flexibility in subsequent steps. The approach successfully controlled the shapes of cardiomyocytes seeded on Matrigel-patterned hydrogels.
Review
Environmental Sciences
Xiaoqing Chang, Yu-Mei Tan, David G. Allen, Shannon Bell, Paul C. Brown, Lauren Browning, Patricia Ceger, Jeffery Gearhart, Pertti J. Hakkinen, Shruti V. Kabadi, Nicole C. Kleinstreuer, Annie Lumen, Joanna Matheson, Alicia Paini, Heather A. Pangburn, Elijah J. Petersen, Emily N. Reinke, Alexandre J. S. Ribeiro, Nisha Sipes, Lisa M. Sweeney, John F. Wambaugh, Ronald Wange, Barbara A. Wetmore, Moiz Mumtaz
Summary: Toxicology has transformed from observational to predictive science with the development of new approaches, such as in vitro assays and in silico models. In vitro to in vivo extrapolation (IVIVE) is gaining acceptance for risk assessment, and there has been a surge of IVIVE publications in the past decade. This review proposes operational definitions for IVIVE, explores its implications in decision-making processes, and highlights the challenges and future needs for its continued development.
Article
Cell Biology
Anna A. Kim, Amanda Nguyen, Marco Marchetti, XinXin Du, Denise J. Montell, Beth L. Pruitt, Lucy Erin O'Brien
Summary: Cytosolic Ca2+ is a highly regulated cellular signal. This study examines Ca2+ dynamics in the adult Drosophila intestine and finds that differentiated cells exhibit distinct patterns of Ca2+ oscillations. Enteroendocrine cells show single-cell oscillations, while enterocytes display long-range waves. Inhibition of gap junctions eliminates Ca2+ oscillations in all cell types. These findings reveal fate-specific modes of Ca2+ dynamics and independent oscillatory dynamics in a coherent epithelium.
JOURNAL OF CELL SCIENCE
(2022)
Review
Toxicology
Xi Yang, Alexandre J. S. Ribeiro, Li Pang, David G. Strauss
Summary: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used in regulatory applications to assess drug-induced cardiotoxicity. However, the predictive capacity of hiPSC-CMs for human cardiac safety in clinical trials is still limited.
TOXICOLOGICAL SCIENCES
(2022)
Review
Biophysics
Liam P. Dow, Toshi Parmar, M. Cristina Marchetti, Beth L. Pruitt
Summary: This article reviews the methods and results of studying how epithelial cells maintain tissue organization and integrity through mechanosignaling and response. Various in vitro approaches have been used to understand the role of mechanics in regulating epithelial tissues. The unique advantages and disadvantages of different simplified model systems are summarized to guide researchers in choosing appropriate experimental systems. In addition, in silico biophysical models informed by in vitro and in vivo observations are highlighted.
BIOPHYSICS REVIEWS
(2023)